Compounds and methods for the treatment of cancer

A process for the synthesis of a compound having a structure of formula (II) or a pharmaceutically acceptable salt thereof

• wherein
• X is S or Se;
• W is O, S, or (R)(R), where each occurrence of R is independently H or a C1-2alkyl;
• n is 0 or 1;
• R1 and R2 are independently C1-10alkyl;
• R3 is —H or C0-6alkyl-COOR6;
• R3′ is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C1-10alkyl, C1-10alkenyl, or C1-10alkynyl;
• R4 is —OH, —H, —CH3, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glutamine;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• and
• R6 is H or C1-10alkyl;
• wherein the melting point of the compound in its crystalline form is greater than 160° C.;
• comprising reacting a compound having a structure of formula
• (R1)(R2)AsCl
• R1 and R2 are independently C1-10alkyl;
• with a compound having a structure of formula (III)
• wherein
• R3 is —H or C0-6alkyl-COOR6;
• R3′ is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C1-10alkyl, C1-10alkenyl, or C1-10alkynyl;
• R4 is —OH, —H, —CH3, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glutamine substituent;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• and
• R6 is H or C1-10alkyl;
• in an aqueous or alcoholic solvent system.

A method for the synthesis of a compound of formula (II)

• wherein
• X is S or Se;
• W is O, S, or (R)(R), where each occurrence of R is independently H or a C1-2alkyl;
• n is 0 or 1;
• R1 and R2 are independently C1-10alkyl;
• R3 is —H or C0-6alkyl-COOR6;
• R3′ is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C1-10alkyl, C1-10alkenyl, or C1-10alkynyl;
• R4 is —OH, —H, —CH3, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glutamine;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• and
• R6 is H or C1-10alkyl;
• wherein a compound having a structure of formula
• (R1)(R2)AsCl
• R1 and R2 are independently C1-10alkyl;
• is reacted with a compound having a structure of formula (III)
• wherein
• R3 is —H or C0-6alkyl-COOR6;
• R3′ is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C1-10alkyl, C1-10alkenyl, or C1-10alkynyl;
• R4 is —OH, —H, —CH3, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glutamine substituent;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• and
• R6 is H or C1-10alkyl;
• in an aqueous or alcoholic solvent system.

A method for the synthesis of a compound of formula (IV)

• wherein
• X is S or Se;
• W is O, S, or (R)(R), where each occurrence of R is independently H or a C1-2alkyl;
• R1 and R2 are independently C1-10alkyl;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• R6 is H or C1-10alkyl;
• R7 is selected from halogen, —OH, C0-6alkyl-COOR6, C1-6alkyl, C1-6alkoxy, amino, amido, cyano, and nitro;
• m is an integer from 0 to 4;
• wherein a compound having a structure of formula
• (R1)(R2)AsCl
• R1 and R2 are independently C1-10alkyl;
• is reacted with a compound having a structure of formula (V)
• wherein
• X is S or Se;
• W is O, S, or (R)(R), where each occurrence of R is independently H or a C1-2alkyl;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• R6 is H or C1-10alkyl;
• R7 is selected from halogen, —OH, C0-6alkyl-COOR6, C1-6alkyl, C1-6alkoxy, amino, amido, cyano, and nitro;
• m is an integer from 0 to 4
• in an aqueous or alcoholic solvent system.

A method for purifying a compound of formula (II) admixed with pyridine hydrochloride,

• wherein
• X is S or Se;
• W is O, S, or (R)(R), where each occurrence of R is independently H or a C1-2alkyl;
• n is 0 or 1;
• R1 and R2 are independently C1-10alkyl;
• R3 is —H or C0-6alkyl-COOR6;
• R3′ is H, amino, cyano, halogen, aryl, aralkyl, heteroaryl, heteroaralkyl, carboxyl, C1-10alkyl, C1-10alkenyl, or C1-10alkynyl;
• R4 is —OH, —H, —CH3, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glutamine;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• and
• R6 is H or C1-10alkyl
• comprising
• (a) combining the compound of formula (II) with enough ethanol to form a slurry,
• (b) agitating the slurry for a period of time, and
• (c) filtering the slurry.

A method for purifying a compound of formula (IV) admixed with pyridine hydrochloride,

• wherein
• X is S or Se;
• W is O, S, or (R)(R), where each occurrence of R is independently H or a C1-2alkyl;
• R1 and R2 are independently C1-10alkyl;
• R5 is —OH, cyano, C1-10alkoxy, amino, O-aralkyl, O-aralkyl, —OC(O)C1-10aralkyl, —OC(O)C1-10alkyl, —OC(O)aryl, or a glycine substituent;
• R6 is H or C1-10alkyl;
• R7 is selected from halogen, —OH, C0-6alkyl-COOR6, C1-6alkyl, C1-6alkoxy, amino, amido, cyano, and nitro;
• m is an integer from 0 to 4;
• comprising
• (a) combining the compound of formula (IV) with enough ethanol to form a slurry,
• (b) agitating the slurry for a period of time, and
• (c) filtering the slurry.